Induction of apoptosis by quercetin: different response of human chronic myeloid (K562) and acute lymphoblastic (HSB-2) leukemia cells
Induction of apoptosis by quercetin: different response of human chronic myeloid (K562) and acute lymphoblastic (HSB-2) leukemia cells
复制标题
DOI：
10.1007/s11010-006-9307-3
复制
发表时间：
2007-02-01
影响因子：
4.3
通讯作者：
Bozzi, Argante
中科院分区：
文献类型：
--
作者：
Brisdelli, Fabrizia;Coccia, Cristina;Bozzi, Argante
本研究表明，25 μ M槲皮素对K562细胞的生长有明显的抑制作用，并有轻微的细胞毒性，而HSB-2细胞几乎不受影响。此外，槲皮素几乎只在前者细胞系中诱导caspase-3和细胞色素c依赖性凋亡。槲皮素对K562细胞G(2)/M期细胞的影响也显著增加，在24 h达到最大峰值（是基础值的4倍）。与HSB-2细胞相比，K562细胞表现出的主要敏感性仅部分归因于其更高的谷胱甘肽含量，从而证实了先前关于暴露于类黄酮的细胞中形成细胞内槲皮素-硫醇毒性加合物的报道。事实上，在诱导细胞内谷胱甘肽增加后，我们在两种细胞系中检测到凋亡细胞的显著增加，在K562细胞中更为明显。相比之下，谷胱甘肽缺失的细胞在两种细胞系中都没有显示出凋亡的减少，这与我们之前的发现和文献数据相矛盾。由于槲皮素的抗氧化或促氧化能力尚未解决的问题，我们研究了这两种性质在我们的实验模型中起作用。有趣的是，槲皮素不仅不产生活性氧，而且还能阻止它们的形成，正如在暴露于氧化剂叔丁基过氧化氢的细胞中观察到的那样，槲皮素是一种有效的氧自由基清除剂。这表明槲皮素在这些细胞系中表现出抗氧化能力大于促氧化能力。
This work shows that 25 mu M quercetin caused a marked inhibition of K562 cells growth together with a mild cytotoxicity, while HSB-2 cells were practically unaffected. Moreover, quercetin induced caspase-3 and cytochrome c-dependent apoptosis almost exclusively in the former cell line. Exposure of K562 cells to quercetin caused also a significant increase of cells in G(2)/M phase that reached the maximum peak at 24 h (4-fold with respect to the basal value). The major sensitivity exhibited by K562 cells was only in part imputable to their higher glutathione content, as compared to HSB-2 cells, thus confirming previous reports describing the formation of intracellular quercetin-thiol toxic adducts in cells exposed to the flavonoid. In fact, after induction of intracellular glutathione increase we detected in both cell lines a significant rise of apoptotic cells, again more marked in K562 cells. By contrast, glutathione-depleted cells, failed to show a decrease of apoptosis in both cell lines, thus contradicting our previous findings and literature data. Since the yet unresolved question about the anti-oxidant or the pro-oxidant capacity of quercetin, we investigated which of these two properties worked in our experimental model. Interestingly, not only quercetin did not produce reactive oxygen species but also prevented their formation, as observed in cells exposed to the oxidizing agent ter-butylhydroperoxide, acting as an efficient oxygen radicals scavenger. This result indicates that quercetin exhibited, in these cell lines, anti-oxidant more than pro-oxidant ability.